Can LASSBio 596 and dexamethasone treat acute lung and liver inflammation induced by microcystin-LR?

The treatment of microcystin-LR (MCYST-LR)-induced lung inflammation has never been reported Hence. LASSBio 596, an anti-Inflammatory drug candidate, designed as symbiotic agent that modulates TNF-alpha levels and inhibits phosphodiesterase types 4 and 5, or dexamethasone were tested in this condition Swiss mice were intraperitoneally (i p) injected with 60 mu l of saline (CTRL) or a sub-lethal dose of MCYST-LR (40 mu g/kg). 6 h later they were treated (i p.) with saline (TOX), LASSB10 596 (10 mg/kg, L596), or dexamethasone (1 mg/kg, 0.1 mL, DEXA). 8 h after MCYST-LR injection, pulmonary mechanics were determined, and lungs and livers prepared for histopathology, biochemical analysis and quantification of MCYST-LR. TOX showed significantly higher lung impedance than CTRL and L596, which were similar. DEXA could only partially block the mechanical alterations. In both TOX and DEXA alveolar collapse and inflammatory cell influx were higher than in CTRL and L596, being LASSB10 596 more effective than dexamethasone. TOX showed oxidative stress that was not present in an and L596, while DEXA was partially efficient. MCYST-LR was detected in the livers of all mice receiving MCYST-LR and no recovery was apparent In conclusion, LASSBio 596 was more efficient than dexamethasone in reducing the pulmonary functional impairment induced by MCYST-LR. (C) 2010 Elsevier Ltd. All rights reserved

Humoral responses and immune protection in mice immunized with irradiated T. gondii tachyzoites and challenged with three genetically distinct strains of T. gondii

Toxoplasma gondii is an obligate intracellular parasite that infects a variety of mammals and birds. T. gondii also causes human toxoplasmosis; although toxoplasmosis is generally a benign disease, ocular, congenital or reactivated disease is associated with high numbers of disabled people. Infection occurs orally through the ingestion of meat containing cysts or by the intake of food or water contaminated with oocysts. Although the immune system responds to acute infection and mediates the clearance of tachyzoites, parasite cysts persist for the lifetime of the host in tissues such as the eye, muscle, and CNS. However, T. gondii RH strain tachyzoites irradiated with 255 Gy do not cause residual infection and induce the same immunity as a natural infection. To assess the humoral response in BALB/c and C57BL/6J mice immunized with irradiated tachyzoites either by oral gavage (p.o.) or intraperitoneal (i.p.) injection, we analyzed total and high-affinity IgG and IgA antibodies in the serum. High levels of antigen-specific IgG were detected in the serum of parenterally immunized mice, with lower levels in mice immunized via the oral route. However, most serum antibodies exhibited low affinity for antigen in both mice strain. We also found antigen specific IgA antibodies in the stools of the mice, especially in orally immunized BALB/c mice. Examination of bone marrow and spleen cells demonstrated that both groups of immunized mice clearly produced specific lgG, at levels comparable to chronic infection, suggesting the generation of IgG specific memory. Next, we challenged i.p. or p.o. immunized mice with cysts from ME49. VEG or P strains of T. gondii. Oral immunization resulted in partial protection as compared to challenged naive mice: these findings were more evident in highly pathogenic ME49 strain challenge. Additionally, we found that while mucosal IgA was important for protection against infection, antigen-specific IgG antibodies were involved with protection against disease and disease pathogenesis. Most antigen responsive cells in culture produced specific high-affinity IgG after immunization, diverse of the findings in serum IgG or from cells after infection, which produced low proportion of high-avidity IgG. (C) 2011 Elsevier B.V. All rights reserved.

Crack Cocaine Use in Barcelona: A Reason of Worry

In Spain, crack cocaine use is silently increasing. In Barcelona, an intentional sample was selected to describe the general characteristics of this consumption. Participants were submitted to an interview and data were analyzed through qualitative research procedures. Users are young males and of low socioeconomic status and formal education. The major pattern of use is compulsive. Illegal income activities are the choice for crack cocaine or money acquisition, increasing individual and social health costs. Polydrug use is a matter of concern. Although these findings can not be generalized, they should be considered for the development of public policies to adequately address crack cocaine users` needs.

Prospective randomized comparison of human oocyte cryopreservation with slow-rate freezing or vitrification

Objective: To compare cryopreservation of mature human oocytes with slow-rate freezing and vitrification and determine which is most efficient at establishing a pregnancy. Design: Prospective randomized. Setting: Academically affiliated, private fertility center. Patient(s): Consenting patients with concerns about embryo cryopreservation and more than nine mature oocytes at retrieval were randomized to slow-rate freezing or vitrification of supernumerary (more than nine) oocytes. Intervention(s): Oocytes were frozen or vitrified, and upon request oocytes were thawed or warmed, respectively. Main Outcome Measure(s): Oocyte survival, fertilization, embryo development, and clinical pregnancy. Result(s): Patient use has resulted in 30 thaws and 48 warmings. Women`s age at time of cryopreservation was similar. Oocyte survival was significantly higher following vitrification/warming (81%) compared with freezing/thawing (67%). Fertilization was more successful in oocytes vitrified/warmed compared with frozen/thawed. Fertilized oocytes from vitrification/warming had significantly better cleavage rates (84%) compared with freezing/thawing (71%) and resulted in embryos with significantly better morphology. Although similar numbers of embryos were transferred, embryos resulting from vitrified oocytes had significantly enhanced clinical (38%) pregnancy rates compared with embryos resulting from frozen oocyte (13%). Miscarriage and/or spontaneous abortion rates were similar. Conclusion(s): Our results suggest that vitrification/warming is currently the most efficient means of oocyte cryopreservation in relation to subsequent success in establishing pregnancy. (Fertil Steril (R) 2010; 94: 2088-95. (C) 2010 by American Society for Reproductive Medicine.)

Anti-Inflammatory Effects of Peritoneal Lavage in Acute Pancreatitis

Objectives: Intraperitoneal administration of trypsin stimulates the production of cytokines from peritoneal macrophages. Removing the pancreatitis-associated ascitic fluid from the peritoneal cavity may decrease the systemic inflammatory response in acute pancreatitis (AP). We investigated the effect of peritoneal lavage on the systemic inflammatory response in severe AP. Methods: Acute pancreatitis was induced in Wistar rats by 5% taurocholate intraductal injection. Peritoneal lavage was performed for 4 hours after onset of AP. At 4 hours after induction of AP, serum samples were assayed for amylase and inflammatory cytokines (tumor necrosis factor alpha, interleukin-6 [IL-6], and IL-10). Expression of pancreatic cyclooxygenase-2 and inducible nitric oxide synthase, liver mitochondrial function, and pulmonary myeloperoxidase activities were determined. Results: Peritoneal lavage after AP led to a decrease in serum levels of tumor necrosis factor alpha and IL-6 and an increase in IL-10. In the pancreas, this treatment reduced cyclooxygenase-2 and inducible nitric oxide synthase expression. Liver mitochondrial dysfunction was also reduced. There were no differences on serum amylase levels and pulmonary myeloperoxidase between groups with AP. Conclusions: Peritoneal lavage has a systemic anti-inflammatory effect in severe AP and may be able to decrease the severity of severe AP.

Meningeal carcinomatosis in breast cancer: prognostic factors and outcome

Meningeal carcinomatosis (MC) occurs in up to 5% of breast cancer patients. Few studies have evaluated prognostic markers in breast cancer patients with MC. Our aim was to describe the treatment of breast cancer patients with MC, and identify prognostic factors related to survival. Sixty breast cancer patients that had a diagnosis of MC between January 2003 and December 2009 were included. The median age was 46 years (range 27-76). Most patients had invasive ductal carcinoma (78.3%) and high histological/nuclear grade (61.7/53.3%). Estrogen and progesterone receptors were positive in 51.7 and 43.3% of patients, respectively, and 15% were HER-2-positive. Symptoms at presentation were headache, cranial nerve dysfunction, seizures, and intracranial hypertension signals. Diagnosis was made by CSF cytology in 66.7% of cases and by MRI in 71.7%. Intrathecal (IT) chemotherapy was used in 68.3% of patients, and 21.6% received a new systemic treatment (chemo- or hormone therapy). Median survival was 3.3 months (range 0.03-90.4). There was no survival difference according to age, nuclear grade, hormonal and HER-2 status, CSF features, sites of metastasis, systemic and IT chemotherapy, or radiotherapy. However, histological grade and performance status had a significant impact on survival in the multivariate analysis. Only four papers have addressed prognostic factors in breast cancer patients with MC in the last two decades. The results of those reports are discussed here. High histological grade and poor performance status seem to impact survival of breast cancer patients with MC. Prospective studies are necessary to clarify the role of IT and systemic treatment in the treatment of those patients.

Endoscopic-guided percutaneous radiofrequency cordotomy

The authors present the first clinical implementation of an endoscopic-assisted percutaneous anterolateral radiofrequency cordotomy. The aim of this article is to demonstrate the intradural endoscopic visualization of the cervical spinal cord via a percutaneous approach to refine the spinal target for anterolateral cordotomy, avoiding undesired trauma to the spinal tissue or injury to blood vessels. Initially, a lateral puncture of the spinal canal in the C1-2 interspace is performed, guided by fluoroscopy. As soon as CSF is reached by the guide cannula (17-gauge needle), the endoscope can be inserted for visualization of the spinal cord and its surrounding structures. The endoscopic visualization provided clear identification of the pial surface of the spinal cord, arachnoid membrane, dentate ligament, dorsal and ventral root entry zone, and blood vessels. The target for electrode insertion into the spinal cord was determined to be the midpoint from the dentate ligament and the ventral root entry zone. The endoscopic guidance shortened the fluoroscopy usage time and no intrathecal contrast administration was needed. Cordotomy was performed by a standard radiofrequency method after refining of the neurophysiological target. Satisfactory analgesia was provided by the procedure with no additional complications or CSF leak. The initial use of this technique suggests that a percutaneous endoscopic procedure may be useful for particular manipulation of the spinal cord, possibly adding a degree of safety to the procedure and improving its effectiveness. (DOI: 10.3171/2010.4.JNS091779)

Tests for ovarian reserve: reliability and utility

Purpose of review This review discusses ovarian reserve tests for ovulation induction and their application in determining fertility capacity, and their current applications to assess risk of natural ovarian failure and to estimate ovarian function after cancer treatment. Recent findings The current arsenal of ovarian reserve tests comprises hormonal markers [basal follicle stimulating hormone, estradiol, inhibin-B, antimullerian hormone (AMH)] and ultrasonographic markers [ovarian volume, antral follicle counts (AFCs)]. These markers have limitations in terms of which test(s) should be used to reliably predict ovarian reserve with regard to accuracy, invasiveness, cost, convenience, and utility. Several studies have correlated sonographic AFCs with serum AMH levels for predicting the ovarian response to ovulation induction protocols during assisted reproduction treatments. Summary Serum AMH levels and AFC are reliable tests for predicting the ovarian response to ovulation induction. However, none of the currently employed tests of ovarian reserve can reliably predict pregnancy after assisted conception. Further, ovarian reserve tests cannot predict the onset of reproductive and hormonal menopause; thus, they should be used with caution for reproductive life-programming counseling. Moreover, there is no evidence to support the use of ovarian reserve tests to estimate the risk of ovarian sufficiency after cancer treatments.

Involvement of circulating platelets on the hyperalgesic response evoked by carrageenan and Bothrops jararaca snake venom

Background: The role of platelets in hemostasis is well known, but few papers have reported their role in pain and edema induced by inflammatory agents. Objective: To evaluate the role of circulating platelets in the local injury induced by two diverse inflammatory agents, Bothrops jararaca venom (Bjv) and carrageenan. Methods: Rats were (i) rendered thrombocytopenic by administration of polyclonal anti-rat platelet IgG (ARPI) or busulfan, or (ii) treated with platelet inhibitors (aspirin or clopidogrel). Edema formation, local hemorrhage and the pain threshold were assessed after intraplantar injection of Bjv or carrageenan in rat hind paws. Additionally, whole platelets or platelet releasate were tested whether they directly induced hyperalgesia. Results: Platelet counts were markedly diminished in rats administered with either ARPI (+/- 88%) or busulfan (+/- 96%). Previous treatment with ARPI or busulfan slightly reduced edema induced by Bjv or carrageenan. Injection of Bjv, but not of carrageenan, induced a statistically significance increase in hemorrhage in the hind paws of thrombocytopenic rats. Remarkably, hyperalgesia evoked by Bjv or carrageenan was completely blocked in animals treated with ARPI or busulfan, or pre-treated with aspirin or clopidogrel. On the other hand, intraplantar administration of whole platelets or platelet releasate evoked hyperalgesia, which was inhibited by pre-incubation with alkaline phosphatase. Conclusions: Thrombocytopenia or inhibition of platelet function drastically reduced hyperalgesia induced by injection of carrageenan or Bjv; moreover, platelets per se secrete phosphorylated compounds involved in pain mediation. Thus, blood platelets are crucial cells involved in the pain genesis, and their role therein has been underestimated.

CO(2) Abdominal Insufflation Decreases Local and Systemic Inflammatory Response in Experimental Acute Pancreatitis

Objectives: Acute pancreatitis (AP) is a serious disease that is amplified by an associated systemic inflammatory response. We investigated the effect of CO(2) pneumoperitoneum on the local and systemic inflammatory response in AP. Methods: Acute pancreatitis was induced in Wistar rats by 5% taurocholate intraductal injection. Carbon dioxide pneumoperitoneum was applied for 30 minutes before the induction of AP. Inflammatory parameters were evaluated in the peritoneum (ascites, cell number, and tumor necrosis factor alpha [TNF-alpha]), serum (amylase, TNF-alpha, interleukin-6 [IL-6], and IL-10), pancreas (myeloperoxidase [MPO] activity, cyclooxygenase 2 and inducible nitric oxide synthase expression, and histological diagnosis), liver, and lung (mitochondria dysfunction and MPO activity). Results: Abdominal insufflation with CO(2) before induction of AP caused a significant decrease in ascites volume, cells, and TNF-alpha in the peritoneal cavity and in serum TNF-alpha and IL-6 but not IL-10 levels. In the pancreas, this treatment reduced MPO activity, acinar and fat necrosis, and the expression of inducible nitric oxide synthase and cyclooxygenase 2. There were no significant differences on serum amylase levels, liver mitochondrial function, and pulmonary MPO between groups. Conclusions: Our data demonstrated that CO(2) pneumoperitoneum reduced pancreatic inflammation and attenuated systemic inflammatory response in AP. This article suggests that CO(2) pneumoperitoneum plays a critical role on the better outcome in patients undergoing laparoscopic pancreatic surgery.